Background/Objectives: Biologic therapies have transformed the management of inflammatory bowel disease (IBD), but their high cost has prompted the introduction of biosimilars. Although switching from biologic originators to biosimilars is increasingly common, real-world evidence remains limited. We aimed to explore the safety and efficacy of switching between biologic originators and biosimilars. Methods: We conducted a retrospective chart review of patients with IBD between 2015 and 2025. Adult patients receiving adalimumab-adaz or adalimumab-atto were included. Patients who were non-medically switched once from adalimumab originator (Humira®) to any biosimilar were classified as group A. Patients who also switched back to originator (multiple switches) were classified as group B. The outcomes of the study were safety and efficacy of the biosimilars. Logistic regression identified switching predictors. Results: A total of 237 patients were included in the study. The number of patients in group A and group B was 208 and 58 patients, respectively. Sustained clinical remission was achieved in 198 (95.4%) of group A and 54 (93.6%) of group B participants. Sustained normalization of inflammatory markers was also comparable, occurring in 190 (91.5%) of group A and 54 (92.3%) of group B participants. No treatment-emergent AEs, infections, or treatment discontinuations were reported in either group (0%). Regression analysis identified older age and prior immunomodulator use as significant predictors of switching. Conclusions: Multiple switches of adalimumab biosimilars can be safely undertaken without increasing the risk of adverse reactions or treatment failure. This study provides meaningful evidence to guide policy and physician confidence in biosimilar interchangeability as a sustainable IBD therapeutic strategy.
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